Researchers from the University of Toronto and other scientific institutions in Canada and South Korea sought to determine why patients given dexmedetomidine experience a reduced incidence of delirium and why it appears to preserve cognition in patients who receive this medication. Dexmedetomidine is currently used to induce sedation in initially intubated and mechanically ventilated patients during treatment in an intensive care setting and for sedation of nonintubated patients prior to and/or during surgical and other procedures.

Lead author Dian-Shi Wang, MD, PhD, University of Toronto, and colleagues teamed up with scientists from the Department of Anesthesia, Sunnybrook Health Sciences Centre, Toronto; The Center for Neuroscience and Connectomics, Korea Institute of Science and Technology, Seoul, South Korea; and the Division of Vision Sciences, Krembil Research Institute, University Health Network, Toronto, to study the impact of dexmedetomidine in preventing cognitive deficits in ICU patients.  

While researchers already knew that dexmedetomidine had these cognitive-protective effects, the study revealed that the mechanism by which cognitive deficits after anesthesia were prevented occurred by reducing neuronal alpha-5 gamma-aminobutyric acid type A (GABAA) receptor expression.

These GABA effects were modulated by an alpha-2 receptor–mediated release of brain-derived neurotrophic factor from astrocytes. Prior to conducting this study, researchers had already recognized that even a single anesthetic administration resulted in a sustained increase in the expression of cell-surface GABAA receptors containing alpha-2 subunits.

When describing the importance of their work, the researchers noted, “Postoperative delirium is associated with poor long-term outcomes and increased mortality. General anesthetic drugs may contribute to delirium because they increase cell surface expression and function of the alpha-5 gamma-aminobutyric acid type A receptors.”

The research team emphasized that these anesthesia-induced effects persist long after the drugs are excreted from the body, thereby suppressing the receptor expression of GABAA receptors containing alpha-2 subunits, and that this action of dexmedetomidine represents a potential new pharmacotherapeutic option to prevent delirium in patients undergoing postoperative and intensive care.

 « Click here to return to Health Systems Update.

​